Pharmacokinetics

Absorption

Distribution

Approximately 95% to 98% bound to plasma proteins. Crosses the placenta and blood-brain barrier.

Metabolism

Extensively metabolized in the liver to a number of metabolites.

Elimination

Plasma half-life is approximately 30 h and the elimination of metabolites may be prolonged. Excreted in the urine and bile in the form of many active and inactive metabolites.

Indications and Usage

For the control of manifestations of the manic type of manic-depressive illness; treatment of schizophrenia and management of psychotic disorders; relief of restlessness and apprehension prior to surgery; adjunct in the treatment of tetanus; management of acute intermittent porphyria; treatment of severe behavioral problems in children 1 to 12 y of age; control of nausea and vomiting; relief of intractable hiccups; for the short-term treatment of hyperactive children who show excessive motor activity with accompanying conduct disorders.

Unlabeled Uses

Treatment of migraine headaches (IM or IV forms).

Contraindications

Comatose states; allergy to product or other phenothiazines; presence of large amounts of other CNS depressants.

Dosage and Administration

Psychiatric (Outpatient)Adults and children older than 12 y

IM 25 mg for prompt control; may repeat in 1 h. PO 25 to 50 mg 3 times daily for prompt control of severe symptoms after initial regimen. May initiate oral dosing with 10 mg 3 to 4 times daily or 25 mg 2 or 3 times daily. After 1 or 2 days, daily dosage may be increased by 20 to 50 mg at semiweekly intervals for more severe cases until patient becomes calm and cooperative.

Children 6 mo to 12 y of age

PO 0.55 mg/kg every 4 to 6 h as needed. IM 0.55 mg/kg every 6 to 8 h as needed.

Psychiatric (Inpatient)Adults and children older than 12 y

PO 25 mg 3 times daily for patients less acutely disturbed. Increase as needed, usually 400 mg/day. For acute schizophrenic or manic states, 500 mg/day is generally sufficient. Up to 2,000 mg/day may be needed, but generally not for extended periods. IM 25 mg initially; may give additional 25 to 50 mg in 1 h. Increase gradually over several days up to 400 mg every 4 to 6 h in severe cases until the patient is controlled.

Children 6 mo to 12 y of age

PO/IM Start low and increase gradually; 50 to 100 mg/day may be needed in severe behavioral disorders or 200 mg/day or more in older children. Up to 5 y of age or 22.7 kg: Do not exceed 40 mg/day IM. 5 to 12 y of age or 22.7 to 45.5 kg: Do not exceed 75 mg/day IM, except in unmanageable cases.

Acute Intermittent PorphyriaAdults and children older than 12 y

PO 25 to 50 mg 3 or 4 times daily. Can usually be discontinued after several weeks, but maintenance therapy may be necessary. IM 25 mg 3 to 4 times daily.

TetanusAdults and children older than 12 y

IM 25 to 50 mg 3 to 4 times daily usually in conjunction with barbiturates. IV 25 to 50 mg diluted to at least 1 mg/mL and administered at rate of 1 mg/min.

Children 6 mo to 12 y of age

IM/IV 0.55 mg/kg every 6 to 8 h. When giving IV, dilute to at least 1 mg/mL and administer at rate of 1 mg per 2 min. In children 22.7 kg or less, do not exceed 40 mg/day; 22.7 to 45.5 kg, do not exceed 75 mg/day except in severe cases.

Nausea and VomitingAdults and children older than 12 y

PO 10 to 25 mg every 4 to 6 h as needed. IM 25 mg. If no hypotension, may give 25 to 50 mg every 4 to 6 h as needed.

PO 0.55 mg/kg every 4 to 6 h as needed. IM 0.55 mg/kg every 6 to 8 h as needed. Do not exceed 40 mg/day up to 5 y of age (or 22.7 kg) or 75 mg/day if 5 to 12 y of age (or 22.7 to 45.5 kg), except in severe cases.

PO 25 to 50 mg 3 to 4 times daily. IM May give 25 to 50 mg if symptoms persist after 2 to 3 days of oral therapy. IV May administer 25 to 50 mg in 500 to 1,000 mL of saline as a slow infusion with patient flat in bed if hiccups persist.

Elderly/Debilitated/Emaciated Patients

Lower initial doses and more gradual adjustments are recommended.

General Advice

Administer tablets as prescribed, without regard to meals. Administer with food if GI upset occurs.

If irritation occurs after IM administration, further IM doses may be diluted with saline or procaine 2%.

Injection must be diluted, following manufacturer's guidelines, before administering IV.

Do not administer injection if particulate matter or marked discoloration are noted. A slight yellowish discoloration is normal and will not alter potency.

If injection is spilled on skin or clothing, rinse area immediately with water to prevent contact dermatitis.

For psychotic disorders, maximum improvement may not be seen for weeks or months.

Use IV route only for severe hiccups, surgery, and tetanus.

Do not mix with other agents in syringe.

When discontinuing therapy, gradual reduction of dosage is recommended.

Storage/Stability

Store tablets and injection between 59° and 86°F. Protect injection from light and freezing.

Drug Interactions

Abiraterone

Plasma concentrations and pharmacologic effects of chlorpromazine may be increased by abiraterone. Avoid concurrent use.

Alcohol

Concurrent use may produce additive effects and hypotension.

Anorexiants (eg, dextroamphetamine)

Coadministration may decrease or abolish the pharmacologic effects of both drugs.

Anticholinergics (eg, atropine)

Additive anticholinergic toxicity may occur. Use with caution. If anticholinergics are required, it may be necessary to adjust the chlorpromazine dosage to produce the maximum therapeutic effect with minimum toxicity.

Anticoagulants, oral (eg, warfarin)

Chlorpromazine diminished the effect of oral anticoagulants.

Anticonvulsants (eg, phenytoin)

Start chlorpromazine at low doses and increase as needed. Chlorpromazine may lower the convulsive threshold; dosage adjustments of anticonvulsants may be necessary. Chlorpromazine may interfere with the metabolism of phenytoin and thus precipitate phenytoin toxicity.

CNS depressants (eg, anesthetics, barbiturates, opioids)

Chlorpromazine prolongs and intensifies the action of CNS depressants. Concurrent use of chlorpromazine with large amounts of CNS depressants is contraindicated. When chlorpromazine is coadministered, approximately 25% to 50% of the usual dosage of such agents is required. When chlorpromazine is not being administered to reduce requirements of CNS depressants, it is best to stop such depressants before starting chlorpromazine treatment. These agents may subsequently be reinstated at low doses and increased as needed.

Epinephrine

Chlorpromazine may reverse the beta-adrenergic effects of epinephrine, producing hypotension and tachycardia. Concurrent use is not recommended.

Guanethidine

Chlorpromazine may counteract the antihypertensive effect of guanethidine and related compounds.

Levodopa

The pharmacologic effects of levodopa may be decreased. Concomitant use is not recommended. If concomitant use is necessary, monitor the patient for reduced levodopa pharmacologic effect.

Lithium

An encephalopathic syndrome has occurred in a few patients treated with lithium plus a neuroleptic. Monitor closely for early evidence of neurologic toxicity and discontinue treatment promptly if such signs appear. Concomitant therapy has also been reported to decrease chlorpromazine levels.

Metoclopramide

Coadministration may increase the risk of extrapyramidal reactions. Coadministration is contraindicated.

Pergolide

The pharmacologic effects of pergolide may be decreased.

Propranolol

Plasma levels of both drugs may be increased. Consider dosage reduction of both agents.

Respiratory

Miscellaneous

Precautions

Warnings

Increased mortality

Elderly patients with dementia-related psychosis treated with antipsychotics are at an increased risk of death. Over the course of a 10-wk controlled trial, the rate of death in drug-treated patients was approximately 4.5% compared with 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either CV (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Chlorpromazine is not approved for the treatment of patients with dementia-related psychosis.

Monitor

Periodically reassess the need for continued treatment. Frequently monitor CBC in patients with preexisting low WBC or a history of drug-induced leukopenia/neutropenia during the first few months of therapy. Carefully monitor patients with neutropenia for signs and symptoms of infection. Monitor patients for signs and symptoms of tardive dyskinesia. Carefully monitor patients who require reintroduction of treatment after NMS because recurrences have been reported. Perform periodic ocular examinations in patients receiving moderate- to high-dose therapy for long durations.

Pregnancy

Pregnancy category undetermined. Neonates exposed to antipsychotics during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery.

Lactation

Excreted.

Children

Do not use in children younger than 6 mo unless considered life-saving. Do not use in conditions for which specific children's dosage is not established.

Elderly

More susceptible to enhanced effects; consider a lower dose.

Renal Function

Use with caution.

Hepatic Function

Use with caution.

Special Risk Patients

Use caution in patients with CV disease, respiratory disorder (eg, severe asthma, emphysema, acute respiratory infection), history of glaucoma, or EEG abnormalities or seizure disorders, or who will be exposed to extreme heat or organophosphorus insecticides.

Abrupt withdrawal

Abrupt withdrawal of high-dose therapy may cause symptoms resembling physical dependence such as gastritis, nausea, vomiting, dizziness, and tremulousness. Avoid sudden discontinuation of therapy if possible. Attempt to gradually reduce dose if a decision to discontinue medication is made.

Antiemetic effect

May mask the signs and symptoms of overdosage of other drugs and obscure the diagnosis and treatment of other conditions, such as intestinal obstruction, brain tumor, or Reye syndrome.

Aspiration

As a result of suppression of cough reflex, aspiration of vomitus is possible.

Bedfast patient

Administer IM dose to patient who is bedfast. Keep patient lying down for at least 30 min after injection to minimize hypotensive effects.

Bone marrow suppression

Patients with bone marrow depression or who have previously demonstrated a hypersensitivity reaction with a phenothiazine should not receive chlorpromazine unless, in the judgment of the health care provider, the potential benefits outweigh the possible risks.

CNS effects

May impair mental or physical abilities, especially during the first few days of therapy. May lower convulsive threshold; dosage adjustments of anticonvulsants may be necessary.

Hematologic effects

Leukopenia/neutropenia and agranulocytosis have been reported.

Hepatic effects

Jaundice usually occurs between second and fourth weeks of treatment; it is considered a hypersensitivity reaction and is usually reversible.

Hyperprolactinemia

Patients treated with antipsychotic agents often have elevation in prolactin levels; however, there is no evidence of increased breast tumor risk.

Long-term use

Consider the possibility of skin pigmentation and ocular changes (corneal and lenticular deposits) when patients are on long-term therapy.

NMS

Has occurred with agents of this class and is potentially fatal. Signs and symptoms are hyperpyrexia, muscle rigidity, altered mental status, irregular pulse, irregular BP, tachycardia, and diaphoresis.

Photosensitivity

Has been reported; avoid unnecessary exposure to the sun.

Tardive dyskinesia

Syndrome of potentially irreversible involuntary body and facial movements may develop. Prevalence highest in elderly patients, especially women. Use the smallest effective dose for the shortest possible time period.

Patient Information

Advise patients, families, or caregivers that the dose will be adjusted periodically until max benefit has been obtained.

Advise patients, families, or caregivers not to change the dose or to stop taking chlorpromazine unless advised by their health care provider.

Instruct patients, families, or caregivers to immediately report fainting or loss of consciousness, palpitations, dizziness, high fever, muscle rigidity or unusual muscle movements, altered mental status, irregular pulse, sore throat or other signs of infection, bleeding or unusual bruising, or yellowing of the skin or eyes.

Advise patients, families, or caregivers to notify their health care provider of any of the following: excessive drowsiness, increased agitation or anxiety, or involuntary body or facial movements.

Advise patients to avoid strenuous activity during periods of high temperature or humidity.

Instruct patients to avoid alcoholic beverages and other depressants while taking chlorpromazine.

Instruct patients to get up slowly from a lying or sitting position and to avoid sudden position changes to prevent postural hypotension. Advise patients to report dizziness with position changes to their health care provider. Caution patients that hot tubs and hot showers or baths may make dizziness worse.

Advise patients to take sips of water, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.

Advise patients that chlorpromazine may cause drowsiness or impaired judgment or thinking skills, and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.

Caution patients that chlorpromazine may cause sensitivity to sunlight and to therefore avoid unnecessary exposure to UV light (eg, sunlight, tanning booths), and to use sunscreen and wear protective clothing when exposed to UV light until tolerance is determined.

Advise patients to report any vision disturbance or change. Patients receiving moderate- to high-dose therapy for long periods of time may need to have periodic eye examinations.